β-casein nanovehicles for oral delivery of chemotherapeutic drug combinations overcoming P-glycoprotein-mediated multidrug resistance in human gastric cancer cells

Bar-Zeev, Maya; Assaraf, Yehuda G.; Livney, Yoav D.

doi:10.18632/oncotarget.8019

Cited by 76 publications

(44 citation statements)

References 58 publications

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“…The data were analyzed using a nonlinear curve fitting of a sigmoidal model (Hill1) with OriginPro 9.0 for doseresponse curve according to Eq. (3) 59 :…”

Section: Cytotoxicity Assaysmentioning

confidence: 99%

Selective eradication of human non-small cell lung cancer cells using aptamer-decorated nanoparticles harboring a cytotoxic drug cargo

2019

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Targeted cancer therapy is currently the leading modality to enhance treatment selectivity and efficacy, as well as to minimize untoward toxicity to healthy tissues. Herein, we devised and studied nanoparticles (NPs) composed of the biocompatible block-copolymer PEG-PCL entrapping the hydrophobic chemotherapeutic drug paclitaxel (PTX), which are targeted to human non-small cell lung cancer (NSCLC) cells. To achieve selective NSCLC targeting, these NPs were decorated with single-stranded oligonucleotide-based S15 aptamers (S15-APTs), which we have recently shown to serve as efficient tumor cell targeting ligands. Prepared without using surfactants, these 15 nm PEG-PCL/PTX NPs entered NSCLC cells via clathrin-mediated endocytosis. These NPs demonstrated efficient encapsulation of PTX, high selectivity to-and potent eradication of human A549 NSCLC cells, with a remarkable half maximal inhibitory concentration (IC 50) of 0.03 μM PTX. In contrast, very high IC 50 values of 1.7, 4.2, 43, 87, and 980 µM PTX were obtained towards normal human bronchial epithelial BEAS2B, cervical carcinoma HeLa, colon adenocarcinoma CaCo-2, neonatal foreskin fibroblast FSE, and human embryonic kidney HEK-293 cells, respectively. These results demonstrate 2-5 orders of magnitude difference in the selective cytotoxicity towards NSCLCs, reflecting a potentially outstanding therapeutic window. Moreover, the dual utility of aptamer-decorated NPs for both drug stabilization and selective tumor targeting was studied by increasing APT concentrations during NP "decoration". The optimal aptamer density on the surface of NPs for selective targeting, for high fluorescence diagnostic signal and for maintaining small particle size to enable endocytosis, was achieved by using 30 nM APTs during NP decoration. Collectively, our findings suggest that these APT-decorated NPs hold great preclinical promise in selective targeting and eradication of human NSCLC cells without harming normal tissues.

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“…The data were analyzed using a nonlinear curve fitting of a sigmoidal model (Hill1) with OriginPro 9.0 for doseresponse curve according to Eq. (3) 59 :…”

Section: Cytotoxicity Assaysmentioning

confidence: 99%

Selective eradication of human non-small cell lung cancer cells using aptamer-decorated nanoparticles harboring a cytotoxic drug cargo

2019

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“…Other models oriented on micellar organization deal with dynamic forms [11], including micellar aggregates studied in the context of membrane proteins [12,13]. Studies of micellar forms and their applications in drug transport can be found in [14][15][16][17][18][19]. Notably, the ability to construct a co-micelle (i.e., …”

Section: Introductionmentioning

confidence: 99%

Application of the Fuzzy Oil Drop Model Describes Amyloid as a Ribbonlike Micelle

Roterman

Banach

Konieczny

2017

Entropy

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Abstract:We propose a mathematical model describing the formation of micellar forms-whether spherical, globular, cylindrical, or ribbonlike-as well as its adaptation to protein structure. Our model, based on the fuzzy oil drop paradigm, assumes that in a spherical micelle the distribution of hydrophobicity produced by the alignment of polar molecules with the external water environment can be modeled by a 3D Gaussian function. Perturbing this function by changing the values of its sigma parameters leads to a variety of conformations-the model is therefore applicable to globular, cylindrical, and ribbonlike micelles. In the context of protein structures ranging from globular to ribbonlike, our model can explain the emergence of fibrillar forms; particularly amyloids.

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“…Cancer multidrug resistance is the term used to describe a phenomenon in which once a cancer develops resistance to one chemotherapeutic drug, it will become resistant to many (or all) other chemotherapeutic drugs (which may or may not have the same mechanism of action). Cancer multidrug resistance has become a problem that cannot be ignored in clinical practice, and many studies are being carried out to nd ways to combat or reverse it [66][67][68][69][70]. Fu et al reported that the proliferation, migration, and invasion of multidrug-resistant human gastric cancer cell line SGC7901/ADR were signi cantly inhibited by an nhexane extract of ELB in a time-and dose-dependent manner: the cell cycle was arrested in the G2/M phase, and cell apoptosis was induced.…”

Section: Gastric Cancermentioning

confidence: 99%

Research Progress on Chemical Constituents and Anticancer Pharmacological Activities of Euphorbia lunulata Bunge

Wang

Xiao²,

Wang

et al. 2020

BioMed Research International

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Euphorbia lunulata Bunge (ELB) is a traditional Chinese medicine possessing the functions of expectoration, cough relief, asthma relief, detoxification, and itching relief. Modern pharmacological studies have showed that ELB exhibits a variety of activities, such as antitumor, antibacterial, and antioxidant activities. In particular, the anticancer activities of ELB have attracted much attention. In this review, we summarize the recent research progress on the chemical constituents and anticancer activities of ELB by searching the PubMed, Web of Science, and China National Knowledge Infrastructure databases. The results show that more than 151 components have been identified from extracts of ELB, including 73 terpenoids, 28 flavonoids, 8 phenylpropanoids, 7 steroids, 19 phenols, and 5 alkaloids. ELB has been shown to exhibit significant inhibitory effects on lung, cervical, gastric, breast, and liver cancers, and its anticancer effects are mainly manifested in the 3 aspects, including cell cycle arrest, cell apoptosis, and inhibition of the migration of cancer cells.

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β-casein nanovehicles for oral delivery of chemotherapeutic drug combinations overcoming P-glycoprotein-mediated multidrug resistance in human gastric cancer cells

Cited by 76 publications

References 58 publications

Selective eradication of human non-small cell lung cancer cells using aptamer-decorated nanoparticles harboring a cytotoxic drug cargo

Selective eradication of human non-small cell lung cancer cells using aptamer-decorated nanoparticles harboring a cytotoxic drug cargo

Application of the Fuzzy Oil Drop Model Describes Amyloid as a Ribbonlike Micelle

Research Progress on Chemical Constituents and Anticancer Pharmacological Activities of Euphorbia lunulata Bunge

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